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Biomedical subjects

G P Taylor

Publications and source records attributed to G P Taylor.

At least 19 recordsLinked to original sources
PubMed2006

How safe is safer sex? High levels of HSV-1 and HSV-2 in female sex workers in London.

Female sex workers in Europe have low levels of sexually transmitted infections, attributable to condom use. The aim of this paper is to describe the seroepidemiology of HSV-1 and HSV-2 in female sex workers in London by using a 15-year prospective study of 453 sex workers. The seroprevalence of HSV-1 was 74.4% and independently associated with birth in a 'transitional country' (OR 5.4, 95% CI 1.61-18.20). The seroprevalence of HSV-2 was 60% and declined over time; it was also independently associated with time in sex work (OR 2.12, 95% CI 1.23-3.65) and birth in a 'developing country' (OR 2.95, 95% CI 1.34-6.48). We show that a cohort of sex workers with extensive condom use and little known sexually transmitted infection have high levels of HSV-1 and HSV-2 infection, suggesting that condoms may not be universally protective. Sex workers are candidates for HSV vaccine efficacy or intervention studies.

Adolescent↗
PubMed2005

New diagnoses of HTLV infection in England and Wales: 2002-2004.

Human T cell lymphotropic viruses (HTLV) are retroviruses transmitted through breastfeeding, sexual contact, blood transfusion and injecting drug use. HTLV is endemic in the Caribbean, and parts of Africa, Japan and South America, with isolated foci in other areas. Infection is life long. Fewer than 5% of those infected progress to one of the HTLV-related diseases, but these are debilitating and often fatal. In England and Wales, laboratory and clinical reports of new HTLV diagnoses are routinely collected, including infections identified by the blood service since the introduction of anti-HTLV testing in August 2002. Between 2002 and 2004, 273 individuals were diagnosed with HTLV: 102 (37%) were male and 169 female (sex was not reported for two). Median ages at diagnosis were 54 and 50 years respectively. Clinical reports were received for 78% (212/273) individuals. Where reported, 58% (116/199) of individuals were of black Caribbean ethnicity and 29% (57/199) white; 87% (128/147) were probably infected heterosexually or through mother-to-child transmission; 45% (66/146) were probably infected in the Caribbean and 40% (59/146) in the United Kingdom. An appreciable number of HTLV infections continue to be diagnosed within England and Wales, with increases in 2002-2003 because of anti-HTLV testing of blood donations. While most infections diagnosed are directly associated with the Caribbean, transmission of HTLV infection is occurring within England and Wales. Specialist care services for HTLV-infected individuals and their families have improved in recent years, but prevention remains limited.

Comparative Study↗
PubMed2004

Clinical implications of stopping nevirapine-based antiretroviral therapy: relative pharmacokinetics and avoidance of drug resistance.

OBJECTIVE: To determine the pharmacokinetics of cessation of nevirapine (NVP) in order to design clinical protocols which will reduce the risk of resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs). METHODS: In a case study, NNRTI genotypic resistance was demonstrated in a patient discontinuing therapy for toxicity. Subsequently, nine patients receiving NVP-containing antiretroviral regimens and stopping treatment were recruited. Patients were advised to continue the nucleoside analogue reverse transcriptase inhibitor (NRTI) backbone for 5 days following cessation of NVP. Plasma NVP concentrations were determined over 7-10 days after the last dose. HIV-1 reverse transcriptase genotyping was performed at viral load rebound (approximately day 21 following cessation) to detect mutations associated with reduced NNRTI sensitivity. RESULTS: The median predicted time for plasma NVP concentration to fall below the inhibitory concentration (IC)(50) of wild-type virus was 168 h (range 108-264 h). De novo genotypic mutations conferring resistance to NRTIs or NNRTIs were not demonstrated following cessation of therapy. CONCLUSIONS: The prolonged elimination half-life of NVP compared with NRTIs, which persists even after 20 weeks of therapy, raises concern over the development of NNRTI resistance if all three drugs are stopped together. Continuation of the NRTI backbone for a further 5 days, allowing the elimination of NVP, may avoid the development of drug resistance.

Anti-HIV Agents↗
PubMed2004

In the shadow of HIV-HTLV infection in England and Wales, 1987-2001.

Like human immunodeficiency virus (HIV), human T-cell leukaemia/ lymphoma viruses (HTLV) I and II are persistent retroviral infections. Once infected, the lifetime risk of developing the HTLV-associated diseases, malignant or inflammatory, is low (approximately 5%). For those affected, however, these diseases are debilitating, with few treatment options and a poor prognosis. Surveillance of HTLV infections by the Communicable Disease Surveillance Centre (CDSC) has been ongoing since serological testing became available in 1986. Testing of blood donations in England and Wales commenced during August 2002 and awareness of HTLV infection is likely to increase. Therefore, a baseline retrospective review of cases prior to 2002 was conducted. The age and sex distribution of identified HTLV cases has differed little over time. Eighty-five per cent of individuals were linked to the Caribbean by birthplace or ethnicity. Though HTLV infection is chronic and incurable, preventive measures are possible. Improved surveillance is needed to support effective prevention activities.

Adult↗
PubMed2002

Pre-eclampsia, antiretroviral therapy, and immune reconstitution.

Antiretrovirals are standard treatment for HIV-1-positive women during pregnancy in the UK, but little is known about maternal or fetal safety. In our cohort study of 214 pregnant women with HIV-1 infection, those who received no antiretroviral therapy had a rate of pre-eclampsia significantly lower (none of 61) than those on triple antiretroviral therapy (8 of 76; odds ratio 15.3, 95% CI 0.9-270, p=0.0087). However, the rate of pre-eclampsia in HIV-1-positive women on treatment did not differ from that in uninfected controls (12 of 214; p=0.2). The association of HIV-1-related immune deficiency with a low rate of pre-eclampsia, and the restoration of this rate in women treated with triple antiretroviral therapy to the expected rate indicates a pivotal role of the immune system in the pathogenesis of pre-eclampsia. The clinical presentation of pre-eclampsia and toxic effects of antiretroviral therapy could overlap and complicate diagnosis and management in these patients.

Adult↗
PubMed2002

Human T cell leukaemia virus type I associated neuromuscular disease causing respiratory failure.

Polymyositis and inclusion body myositis have rarely been described in association with human T cell leukaemia virus type I (HTLV-I) infection. Most of such patients have coexisting HTLV-I associated myelopathy (HAM). Two patients with HTLV-I infection, myopathy, and respiratory failure are described. The muscle biopsy specimen of the first patient bore the histological features of inclusion body myositis and there was no evidence of concurrent myelopathy. The second patient had HAM, and her muscle biopsy showed non-specific myopathic and neuropathic changes. Both patients developed respiratory muscle weakness over eight years after diagnosis of myopathy, leading to hypercapnic respiratory failure requiring mechanical ventilatory support. Respiratory failure as a complication of HTLV-I associated myopathy has not previously been described.

Biopsy↗
PubMed2001

Pooling of samples for seroepidemiological surveillance of human T-cell lymphotropic virus types I and II.

We evaluated a straight forward pooling strategy for antibody screening of HTLV-I/II, using panels of sera from various parts of the world including a total of 43 HTLV-I and 54 HTLV-II positive specimens. Four antibody screening assays were included in the evaluation: the HTLV-I/II GE 80/81 (Murex Diagnostics), the HTLV-I/HTLV-II Ab Capture ELISA (Ortho Diagnostics), the HTLV-I/II ELISA 3.0 (Genelabs Diagnostics) and the Serodia HTLV-I (Fujirebio). The Murex and Ortho assays represent a new generation of HTLV screening tests with a sandwich format incorporating both HTLV-I and HTLV-II synthetic and/or recombinant peptide antigens. The Genelabs assay is an indirect ELISA with recombinant HTLV-I and -II antigens and Serodia is a particle agglutination assay with HTLV-I whole viral lysate. Each HTLV-positive sample was included in pools of 1/1 up to 1/16, in two-fold steps made in normal HTLV-negative blood donor serum from one up to nine donors. For HTLV-I, with the exception of one false negative sample in dilution 1/16 with Genelabs ELISA, all assays were positive at all dilutions. The Murex assay had absorbance values at maximum levels for all samples at all dilutions. The other assays had gradually decreasing absorbance values although clearly above cut-off. For HTLV-II, the Murex assay correctly detected all samples to dilution 1/16 despite gradually decreasing signals. The Serodia assay had 100% sensitivity to dilution 1/4 while at 1/8 and 1/16 it decreased 82 and 80%, respectively. The Genelabs ELISA had gradually decreasing sensitivity for HTLV-II from 98 (1/1) to 33% (1/16) while the Ortho assay detected all specimens at all dilutions in a limited set of samples tested. Taken together, this evaluation has shown that pooling of samples may be an appropriate strategy for serosurveillance of HTLV. It is, however, crucial to limit the number of samples and to choose assays that allow the dilution caused by the pooling. Using the best performing assays in this evaluation for pools of e.g. five samples would leave a reasonable safety margin.

Agglutination Tests↗
PubMed2001

High production of interferon gamma but not interleukin-2 by human T-lymphotropic virus type I-infected peripheral blood mononuclear cells.

The transactivator protein of human T-lymphotropic virus I (HTLV-I), Tax, has been associated with the up-regulation of several host cell genes, including interleukin 2 (IL-2), the IL-2 receptor-alpha (IL-2Ralpha) chain (CD25), interferon gamma (IFN-gamma), and tumor necrosis factor (TNF). It has been proposed that an IL-2/CD25 autocrine loop plays a part in maintaining the very high proviral loads often found in HTLV-I infection. Furthermore, abnormal production of inflammatory cytokines might contribute to the pathogenesis of the inflammatory diseases associated with HTLV-I infection. However, there has been no study of the expression of these genes in freshly isolated peripheral blood mononuclear cells (PBMCs) naturally infected with HTLV-I. In the present study, flow cytometry was used to determine which cytokines are produced by freshly isolated PBMCs that spontaneously express the HTLV-I Tax protein. Surprisingly, the results show that intracellular Tax expression is associated with rapid up-regulation of IFN-gamma but not TNF or IL-2. A proportion of HTLV-I-infected cells express both IFN-gamma and the surface markers of effector memory cells. Such cells are capable of migration through peripheral tissues and could therefore contribute to the inflammation seen in diseases such as HTLV-I-associated myelopathy/tropical spastic paraparesis. (Blood. 2001;98:721-726)

Cytokines↗
PubMed2001

The effect of implantation of aortic stents on compliance and blood flow. An experimental study in pigs.

Balloon dilation of coarctation of the aorta has been found to be an effective modality for treatment. Recently, in the older child and adult, implantation of endovascular stents has been considered a clinical alternative to dilation alone. Little is known, however, of the effect of implantation of stents on aortic compliance. To investigate this impact of implantation, we studied 18 piglets, divided into experimental and control groups. At median weight of 14 kg, 2 pairs of ultrasonic crystals were implanted on the aortic wall. After 1 week, all animals underwent catheterization. In the experimental group, a 3 cm long balloon expandable stent was implanted in the descending thoracic aorta between the pairs of crystals. Measurements of arterial pressure and dimensions were performed before implantation and immediately thereafter, and at follow-up catheterization. The index of stiffness, beta, and the the elastic modulus of aortic pressure-strain, were calculated as indexes of arterial compliance. The change in compliance during the period of study was not different between groups. At follow-up, no difference was observed between groups in the velocity of the aortic pulse wave, the augmentation index, or the maximum velocity of flow of blood. The stents remained patent and did not affect aortic growth or medial wall thickness. There was no difference between groups in levels of plasma renin activity and serum aldosterone. In this animal model studied over the short term, therefore, implantation of stents does not affect aortic compliance. Further studies are required to elucidate the long term effects of stents on the hemodynamics affecting the aortic wall and local flow dynamics.

Animals↗
PubMed2001

Interferon alpha and zidovudine therapy in adult T-cell leukaemia lymphoma: response and outcome in 15 patients.

Adult T-cell leukaemia lymphoma (ATLL) is an aggressive disease caused by the human T-lymphotropic virus 1 (HTLV-I) with a short survival. Responses to interferon alpha (IFN-alpha) and zidovudine (AZT) have been documented but not with long-term follow-up. We treated 15 ATLL patients with IFN and AZT. Eleven patients had acute ATLL, two had lymphoma and two smouldering ATLL, with progression. The main features were: organomegaly (14), skin lesions (10), high white blood cell (WBC) count (11) and hypercalcaemia (9). Eleven patients had previously received chemotherapy and one had received an autograft. At the time of the study, seven patients had progressive disease and eight were in partial or complete clinical remission. Responses (PR) lasting 2+ to 44+ months were seen in 67%; 26% did not respond (NR) and one patient was not evaluable. Hypercalcaemia predicted a poor outcome but differences were not significant. Eight of the 15 patients have died 3-41 months from diagnosis. Median survival for the 15 patients was 18 months. Survival of the NR ranged from 4 to 20 months; six PR patients are alive 8-82 months from diagnosis. The differences in survival between NR (median: 6 months) and PR (55% of patients alive at 4 years) were statistically significant (P = 0.002). In conclusion, IFN and AZT improves the outcome of ATLL patients and helps maintain responses.

Adult↗
PubMed2001

Guidelines for the management of HIV infection in pregnant women and the prevention of mother-to-child transmission.

AIMS OF THE GUIDELINES: These guidelines, drawn up by a multidisciplinary group of clinicians and lay workers active in the management of pregnant women infected with HIV, aim to give up-to-date information on interventions to reduce the risk of mother to child transmission of the virus. The evidence on the use of interventions to prevent mother to child transmission of HIV has been graded according to the strength of the data as per the definitions of the US Agency for Health Care Policy and Research [1]. Weighted evidence on the use of combination antiretroviral therapy (ART) for the treatment of HIV infection per se is presented in the BHIVA guidelines for adults [2,3]. The highest level evidence (i.e. randomised controlled trials (RCTs) or large, well conducted meta-analyses) is only available for formula feeding, prelabour caesarean section and zidovudine monotherapy. The need to treat mothers for HIV infection has led to the widespread use of ART in pregnancy which in turn results in new questions such as how to deliver when the mother, on therapy, has no detectable plasma viraemia with the most sensitive assays. In addressing many common and/or difficult clinical scenarios in the absence of 'best evidence' the guidelines rely heavily on 'expert opinion'. Recommendations for management are given in the section on clinical scenarios, and summarized in Table 3. An expanded version of these guidelines with an appendix on safety and toxicity data is available on the BHIVA website http://www.bhiva.org. The authors are available to discuss individual cases.

Adult↗
PubMed2001

Experience of nevirapine use in a London cohort of HIV-infected pregnant women.

OBJECTIVE: To describe the experience of four London HIV centres prescribing nevirapine (NVP) to HIV-1 infected pregnant women with respect to immunological and virological response, tolerability and pregnancy outcome. METHODS: We identified all HIV-1-infected women who received NVP as part of a triple antiretroviral regimen during pregnancy between January 1997 and September 1999. Laboratory results, clinical events, side-effects and pregnancy outcome were abstracted using a standardized proforma from the medical records. RESULTS: Forty-six women were identified, 85% of whom were black African. At initiation of NVP, the median age was 29 years and the median baseline CD4 cell count and viral load were 242 cells/microL and 4.15 log10 copies/mL, respectively. Thirty-two out of 36 women who had a plasma sample obtained at, or just prior to, delivery had an undetectable viral load (< 50 to < 400 copies/mL). Adverse events that were definitely attributed to NVP included a generalized rash (n = 2) and hepatitis (n = 2). Obstetric complications occurred in nine women (19.5%), which was not statistically different (P = 0.36) from that found in a historical (1990-96) control group 7/51 (14%). The rate of preterm delivery (13%) was similar to that previously reported in HIV-1 infected pregnant women (18%). CONCLUSIONS: NVP (as part of highly active antiretroviral therapy) reduced plasma viraemia to below the limit of detection in 89% of women. It was generally well tolerated and clinical and laboratory adverse events were infrequent. There was no evidence of an increase in obstetric complications including preterm delivery during the second and third trimesters of pregnancy.

Adult↗
PubMed2001

In vivo selection of T-cell receptor junctional region sequences by HLA-A2 human T-cell lymphotropic virus type 1 Tax11-19 peptide complexes.

Using HLA-peptide tetrameric complexes, we isolated human T-cell lymphotrophic virus type 1 Tax peptide-specific CD8(+) T cells ex vivo. Antigen-specific amino acid motifs were identified in the T-cell receptor Vbeta CDR3 region of clonally expanded CD8(+) T cells. This result directly confirms the importance of the CDR3 region in determining the antigen specificity in vivo.

Amino Acid Motifs↗
PubMed2001

Is first trimester exposure to the combination of antiretroviral therapy and folate antagonists a risk factor for congenital abnormalities?

OBJECTIVES: To assess use of antiretroviral therapy (ART) by HIV positive pregnant women in London since 1994 and the risk of congenital abnormalities associated with multidrug exposure during the first trimester of pregnancy. METHODS: Retrospective multicentre study of medical, obstetric, and paediatric notes of all mother-infant pairs, where the mother was known to be HIV infected before delivery, using a standardised proforma. RESULTS: In this study of 195 mother-infant pairs, use of ART during any stage of pregnancy increased from 33.3% in 1994 to 92.5% in 1999 (p=0.01, trend). First trimester exposure increased from 0% in 1994 to 27.5% in 1999 (p=0.00045, trend). Congenital malformations were observed in nine infants (4.6%). Compared with infants not exposed to ART or folate antagonists during the first trimester (n=148), exposure to both ART and folate antagonists during the first trimester (n=13) was associated with an increased risk of congenital abnormalities (4% v 23.1%; OR 7.10, 95% CI 1.5, 34.2). No malformations were observed in the 34 children exposed to either ART or folate antagonists alone during the first trimester. CONCLUSION: An increasing number of HIV infected women conceived while on ART. Although there is no evidence of teratogenicity caused by ART if given alone during the first trimester, exposure to the combination of ART and folate antagonists was associated with a significantly higher risk of congenital abnormalities in this cohort.

Abnormalities, Drug-Induced↗